International patent application no WO 96/24355 decribes pharmaceutical compositions comprising a topically acceptable antiviral substance and an antiinflammatory glucocorticoid in a pharmaceutically acceptable carrier. The carriers disclosed in this application comprise conventional formulations for each of the respective active agents, that is a conventional antiviral formulation is combined with a conventional glucocorticoid formulation. Such combined formulations have a large number of ingredients, with potential for interreacting with each other, leading to unknown stability and physicochemical characteristics.
European patent application no. EP 44543 relates to oil in water formulations of the acyclic nucleoside antiviral agent acyclovir and describes that effective topical penetration necessitates that the carrier comprises at least 30 weight percent, preferably at least 40 weight percent propylene glycol. This formulation, denoted the MAC formulation, forms the basis of the most widely marketed topical acyclovir preparation.
International patent application no WO 91/11187 relates to oil in water or aqueous topical formulations of the acyclic nucleoside antiviral agent penciclovir. These formulations must comprise at least 30 weight percent, preferably at least 35 weight percent, propylene glycol. European patent application no. EP 416 739 relates to topical formulations of penciclovir comprising at least 30 weight percent propylene glycol and a decyl methyl sulfoxide emulsifier. International patent application no. WO 93/00905 relates to topical formulations of penciclovir comprising at least 30 weight percent, preferably at least 35 weight percent, propylene glycol and a cetomacrogol 1000 emulsifier.
Formulation of a combination product comprising a strongly lipophilic component such as hydrocortisone and a moderately lipophobic component such as an acyclic nucleoside analogue is difficult in the case of conventional pharmaceuticals, but is even more difficult in the case of a topical preparation where release rates of the active ingredients into the target tissue must be taken into account. As described in the publications in the two paragraphs immediately above, it has hitherto been regarded essential to utilise a high level of propylene glycol when formulating acyclic nucleosides in order to achieve adequate penetration of the antiviral agent into the skin or dermal mucosa. We have discovered, however, that while conventional, high concentration propylene glycol carriers can be used to prepare efficacious antiviral compositions within the scope of the above mentioned WO 96/24355 (that is compositions comprising a glucocorticoid and an antiviral agent), these conventional carriers result in the product having an undesirably short shelf life and less than optimal antiviral and therapeutic performance.